Maternally administered melatonin differentially regulates lipopolysaccharide‐induced proinflammatory and anti‐inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain

Abstract: Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including intra‐uterine fetal death and intra‐uterine growth retardation. In the LPS model, tumor necrosis factor alpha (TNF‐ α ) is the major mediator leading to intra‐uterine fetal death and intra‐uterine growth retardation. Interleukin (IL)‐10 protects rodents against LPS‐induced intra‐uterine fetal death and intra‐uterine growth retardation. Melatonin is an immunomodulator. In the present study, we investigated the effect of maternally administered melatonin on LPS‐induced proinflammatory and anti‐inflammatory cytokines in maternal serum, amniotic fluid, fetal liver and fetal brain. The time pregnant mice were injected with melatonin [5.0 mg/kg, intraperitoneal (i.p.)] 30 min before LPS (500 μ g/kg, i.p.) on gestational day 17. As expected, TNF‐ α , IL‐1 β , IL‐6 and IL‐10 were obviously increased in maternal serum and amniotic fluid in response to LPS. In addition, maternal LPS exposure significantly increased the levels of TNF‐ α , IL‐1 β , IL‐6 and IL‐10 in fetal liver, and TNF‐ α and IL‐10 in fetal brain. Melatonin pretreatment significantly attenuated LPS‐evoked elevation of TNF‐ α in maternal serum. On the contrary, melatonin aggravated LPS‐induced increase in IL‐10 in maternal serum. Melatonin had no effect on LPS‐evoked IL‐1 β and IL‐6 in maternal serum and amniotic fluid. Interestingly, maternally administered melatonin also significantly attenuated LPS‐evoked elevation of TNF‐ α in fetal brain, whereas the indole aggravated LPS‐induced increase in IL‐10 in fetal liver. Taken together, these results indicate that maternally administered melatonin differentially regulates LPS‐induced proinflammatory and anti‐inflammatory cytokines in maternal serum, amniotic fluid, fetal liver, and fetal brain.